Eosinophilic gastrointestinal diseases (EGID) are a spectrum of diseases characterized by eosinophilic inflammation of the gastrointestinal tract. In the past decade, there has been a increase in the incidence of EGID. EGID, including eosinophilic gastroenteritis (EG) and eosinophilic esophagitis, are commonly associated with food and aeroallergen hypersensitivity. Many EGID patients have numerous food allergies, and in some patients an amino acid based elemental diet is an effective treatment. This suggests that EGID pathogenesis is due to food allergen driven eosinophilic inflammation. At present, there are major gaps in our understanding of, and ability to effectively treat these diseases. To address both treatment and pathogenesis questions, we have recently completed a clinical trial of omalizumab (therapeutic monoclonal anti-IgE) for eosinophilic gastroenteritis. This study asks two major questions: 1. are anti-IgE therapeutics of clinical utility in eosinophilic gastrointestinal diseases, 2. is the eosinophilic inflammation characteristic of EGID an IgE dependent process? [unreadable] [unreadable] Preliminary analysis of the study demonstrates that omalizumab was well tolerated by all subjects. Omalizumab treatment was effective in blocking IgE in EG patients as shown by a 100-1000 fold shift in allergen driven basophil activation and by reductions in free IgE. Omalizumab treatment caused a significant drop in peripheral blood eosinophilia and in subjects? EG symptoms. Current work is focused on analysis of gut biopsies to examine the effect of omalizumab on eosinophilic infiltration.